The mechanism of action of compounds that regulate cyclic AMP metabolism will be investigated. Emphasis will be placed on neurohormones and other chemical agents known to influence cyclic AMP in braincatecholamines, adenosine, and prostaglandin E1. Representative peptide hormones will also be utilized. Analysis of cyclic AMP concentrations and adenylate cyclase activity will be performed in hybrid somatic cells. The pattern of inheritance of hormonal responses will be determined in hybrids formed between parents with (positive) and without (negative) the response in question. Positive and negative hybrid cells will be analyzed where possible for their content of receptors and for the adenylate cyclase derived from individual parental cells forming the hybrid. In this way, the biochemical and genetic relationship of receptor and cyclase will be studied, and the relevance of "receptor" binding activities will be evaluated. Clones will be sought that are deficient in unknown components of the response mechanism. These studies should aid in elucidation of essential components of the response system and of the genetic mechanisms used to determine specificity of cellular response to neurohormones. Clones are available that display large cyclic AMP responses to adenosine and that show potentiation between adenosine and other stimulators. This pattern is similar to that of brain and has not been seen previously in simpler systems. The mechanism of this potentiative interaction will be sought, as will its relevance to the similar phenomenon observed in brain.